This invention relates to the use of a laminated film to form blister packs in the blisters of which bodies such as fast dissolving dosage forms are cast. Such blister packs typically comprise polymeric films in which the blisters are heat formed. The present invention is particularly concerned with the use of laminated films in which a metal foil is sandwiched between two polymeric layers.
Blister films are particularly suited for the casting of frangible bodies which comprise some pharmaceuticals. These bodies are commonly made using lyophilization or freeze-drying processes, but alternative techniques such as those including a solid state dissolution stage are also used. The liquid material of the body is poured into the blister or blisters, and then subjected to various treatments while still in the blisters. The products remain in the blister until they are ready for consumption and at this stage they are readily extractable.
Polymeric blister films suffer from the disadvantage of being permeable, with the consequence that however well the individual blisters are sealed, there is always a potential storage problem if the contents of the blister must be protected from the surrounding atmosphere. With the above points in mind, laminated blister films have been developed in which a metal foil is sandwiched between polymeric films on either side. Such films are less permeable than all-polymeric films, but some known films can become distorted when subjected to heat treatments, generating irregularities in the cast products and making subsequent handling of the blister pack more difficult. Although some laminated films have been developed which are more stable under heat treatment; see our published European Patent Specification Nos. 0 646 367 and 0 710 101, generally these laminated films are not suitable for the hot-forming of blisters therein. The metal foil core, normally of aluminum, is much better suited to cold forming.
There is currently a strong demand for products cast in blister films as described above to bear some indelible marking. To meet this demand, a hot formed blister can readily be adapted to bear indicia on its internal surface, which indicia are then reflected in the respective surface of the cast dosage form. However, with laminated foils of the kind to which this invention relates, it is difficult if not impossible to create indicia on the inner face of the blister base simultaneously with the formation of the blister itself.
In the present invention, a laminated film comprising a metal foil and a polymeric film on either side thereof is cold formed to define one or more blisters, and the base of the blister is then tamped with indicia, in two discrete stages. The blister is formed in the first stage using a standard technique of advancing a pin in a direction transverse relative to the plane of the film. However, according to the invention, once the blister forming stage is completed, indicia are stamped into the base of the blister in the second stage by advancing a die from one side thereof to clamp the blister base against a mold held against the other side. The direction of the die and disposition of the die and mold may be selected such that the indicia project inwardly or outwardly from the blister base.
Thus, there is disclosed a method of forming a laminated film comprising a metal foil and a polymeric layer on either side of the foil with at least one blister, the base of which bears projecting indicia for molding into a body cast therein, which method comprises cold-forming the blister by advancing a pin in a direction transversely relative to the plane of the film; and stamping the indicia into the base of the blister so formed by advancing a die in the opposite direction against a mold held against the inner face of the blister base.
There is further disclosed a method of forming a laminated film comprising a metal foil and a polymeric layer on either side of the foil with at least one blister, the base of which bears projecting indicia for molding into a body cast therein, which method comprises cold-forming the blister by advancing a pin in a direction transversely relative to the plane of the film; and stamping the indicia into the base of the blister so formed by advancing a die in the same direction against a mold held against the outer face of the blister base.
There is also disclosed a process for manufacturing a cast product comprising forming a blistered laminated film and casting the product in at least one of the blisters so that the indicia stamped into the blister base is reproduced on the corresponding face of the cast product.
Normally, in the practice of the invention the pin used in the formation of the blister itself will be a standard item with a plane flat end face across which the base of the blister is stretched. However, there can be circumstances in which the end face of the pin can be other than flat; for example, it can have the form of a shallow cone to assist in determining the manner in which the blister base is stretched. The end face of the pin can also have formed therein the mold against which a die is advanced to emboss the indicia into the blister base. However, it is normally preferred that during the initial blister formation step there is a continuous surfacing contact with the blister film across the end face of the pin and accordingly, if the mold is there, it will be filled or covered by a suitable blank. Alternatively of course, a quite different pin can be used and particularly in this variant, the blister formation step and the indicia formation step are conducted at different stations, although normally in the same machinery.
As noted above, the indicia formation step is quite separate from the blister formation step completed first, although both are cold forming steps. In some respects, the indicia formation step enables the laminates of the blister film itself to relax, and as a consequence the overall strength of the film and the blister itself can be enhanced.
A variety of arrangements and orientations of the die and mold in the indicia formation step can be adopted. For example, a die can be mounted in the pin used in the blister formation step, and advanced therefrom against the mold after the blister formation step is completed. In another arrangement, the mold can be formed in what is effectively a fixed body against which the blister if formed, with the die being moved to clamp the blister base against and into the mold thereafter.
Again as noted above, the present invention is particularly suitable for use in the manufacture of pharmaceutical products of a delicate construction, such as a fast dissolving dosage form, marketed by R. P. Scherer, Inc. of Basking Ridge, N.J. (USA) under the trademark Zydis(copyright). By providing a means by which a permanent marking can be applied to such products, it is felt that a significant advance has been made.